Passive transfer of collagen XVII-specific antibodies induces sustained blistering disease in adult mice

被引:10
作者
Chiriac, Mircea Teodor [1 ,2 ]
Licarete, Emilia [1 ,2 ]
Sas, Alexandra Gabriela [2 ]
Rados, Andreea Maria [2 ]
Lupan, Iulia [1 ,2 ]
Chiriac, Anca Mirela [3 ]
Speth, Hilda [2 ]
Pop-Vancia, Vlad [2 ]
Domsa, Iacob [4 ]
Sesarman, Alina [5 ]
Popescu, Octavian [1 ,2 ,6 ]
Sitaru, Cassian [5 ,7 ]
机构
[1] Univ Babes Bolyai, Dept Biol, R-3400 Cluj Napoca, Romania
[2] Univ Babes Bolyai, Interdisciplinary Res Inst Bionanosci, Mol Biol Ctr, R-3400 Cluj Napoca, Romania
[3] Univ Med & Pharm, Med Clin 3, Cluj Napoca, Romania
[4] Univ Med & Pharm, Med Clin 4, Cluj Napoca, Romania
[5] Univ Freiburg, Ctr Biol Signalling Studies BIOSS, D-79106 Freiburg, Germany
[6] Romanian Acad, Inst Biol, Bucharest, Romania
[7] Univ Freiburg, Dept Dermatol, Freiburg, Germany
关键词
Autoimmunity; Collagen XVII; Inflammation; Skin; BULLOUS-PEMPHIGOID ANTIGEN; DERMAL-EPIDERMAL SEPARATION; HUMAN AUTOANTIBODIES; HERPES-GESTATIONIS; SERUM-LEVELS; COMPLEMENT; INDUCTION; BP180; PROTEIN; MODEL;
D O I
10.1186/1750-1172-8-17
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background: Bullous pemphigoid is a subepidermal blistering disorder associated with tissue-bound and circulating autoantibodies directed mainly to the hemidesmosomal component collagen XVII. While recapitulating the main immunopathological features of the human disease, frank skin blistering does not develop in the absence of skin rubbing in experimental pemphigoid models that have been established in neonatal mice. Moreover, due to their experimental design they only allow for short-term disease observation. In the present study we aimed to establish a model that reproduces the frank skin blistering seen in patients and allows for longer observation times. Methods: Rabbit and sheep antibodies specific to several fragments of collagen XVII were generated and the purified antibodies were passively transferred into adult mice. Results: Collagen XVII-specific IgG bound to the basal membrane of the skin and mucous membranes activating murine complement in vivo. Mice injected with collagen XVII-specific antibodies, in contrast to mice receiving control antibodies, developed frank skin blistering disease, reproducing human bullous pemphigoid at the clinical, histological and immunopathological levels. Titres of circulating IgG in the serum of mice correlated with the extent of the clinical disease. Mice receiving sheep antibodies specific to murine collagen XVII showed an early onset and a more active disease when compared to litter mates receiving specific rabbit antibodies. Conclusion: This novel animal model for bullous pemphigoid should facilitate further investigations of the pathogenesis of bullous pemphigoid and the development of innovative therapies for this disease.
引用
收藏
页数:10
相关论文
共 46 条
[1]  
Anhalt G J, 1987, Clin Dermatol, V5, P117, DOI 10.1016/0738-081X(87)90056-3
[2]   INDUCTION OF PEMPHIGUS IN NEONATAL MICE BY PASSIVE TRANSFER OF IGG FROM PATIENTS WITH THE DISEASE [J].
ANHALT, GJ ;
LABIB, RS ;
VOORHEES, JJ ;
BEALS, TF ;
DIAZ, LA .
NEW ENGLAND JOURNAL OF MEDICINE, 1982, 306 (20) :1189-1196
[3]   PATHOGENIC EFFECTS OF BULLOUS PEMPHIGOID AUTOANTIBODIES ON RABBIT CORNEAL EPITHELIUM [J].
ANHALT, GJ ;
BAHN, CF ;
LABIB, RS ;
VOORHEES, JJ ;
SUGAR, A ;
DIAZ, LA .
JOURNAL OF CLINICAL INVESTIGATION, 1981, 68 (04) :1097-1101
[4]   INCIDENCE AND DISTRIBUTION OF SUBEPIDERMAL AUTOIMMUNE BULLOUS SKIN DISEASES IN 3 FRENCH REGIONS [J].
BERNARD, P ;
VAILLANT, L ;
LABEILLE, B ;
BEDANE, C ;
ARBEILLE, B ;
DENOEUX, JP ;
LORETTE, G ;
BONNETBLANC, JM ;
PROST, C .
ARCHIVES OF DERMATOLOGY, 1995, 131 (01) :48-52
[5]   NADPH oxidase is required for neutrophil-dependent autoantibody-induced tissue damage [J].
Chiriac, M. T. ;
Roesler, J. ;
Sindrilaru, A. ;
Scharffetter-Kochanek, K. ;
Zillikens, D. ;
Sitaru, C. .
JOURNAL OF PATHOLOGY, 2007, 212 (01) :56-65
[6]   Demonstration of Epitope-Spreading Phenomena in Bullous Pemphigoid: Results of a Prospective Multicenter Study [J].
Di Zenzo, Giovanni ;
Thoma-Uszynski, Sybille ;
Calabresi, Valentina ;
Fontao, Lionel ;
Hofmann, Silke C. ;
Lacour, Jean-Philippe ;
Sera, Francesco ;
Bruckner-Tuderman, Leena ;
Zambruno, Giovanna ;
Borradori, Luca ;
Hertl, Michael .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2011, 131 (11) :2271-2280
[7]   ISOLATION OF A HUMAN EPIDERMAL CDNA CORRESPONDING TO THE 180-KD AUTOANTIGEN RECOGNIZED BY BULLOUS PEMPHIGOID AND HERPES-GESTATIONIS SERA - IMMUNOLOCALIZATION OF THIS PROTEIN TO THE HEMIDESMOSOME [J].
DIAZ, LA ;
RATRIE, H ;
SAUNDERS, WS ;
FUTAMURA, S ;
SQUIQUERA, HL ;
ANHALT, GJ ;
GIUDICE, GJ .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 86 (04) :1088-1094
[8]  
Döpp R, 2000, J AM ACAD DERMATOL, V42, P577, DOI 10.1016/S0190-9622(00)90168-3
[9]   ABSENCE OF SPECIFIC HISTOLOGIC-CHANGES IN GUINEA-PIG SKIN TREATED WITH BULLOUS PEMPHIGOID ANTIBODIES [J].
GAMMON, WR ;
BRIGGAMAN, RA .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1988, 90 (04) :495-499
[10]   CLONING AND PRIMARY STRUCTURAL-ANALYSIS OF THE BULLOUS PEMPHIGOID AUTOANTIGEN BP180 [J].
GIUDICE, GJ ;
EMERY, DJ ;
DIAZ, LA .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1992, 99 (03) :243-250